Back to resultsINC280 in Healthy Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function
Primary Purpose
Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
INC280
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Impairment focused on measuring hepatic impairment,, INC280,, Oral cMET Inhibitor,, Non-Cancer
Eligibility Criteria
Inclusion Criteria (all groups):
- Female subjects must be postmenopausal or sterile
- Good health, as determined by absence of clinically significant findings in medical history, physical examination, vital signs, and ECGs, unless it is consistent with known clinical disease for hepatic impairment subjects
- Adequate organ function and normal laboratory tests, unless it is consistent with known clinical disease for hepatic impairment subjects
- Body Mass Index (BMI) of 18- 36 kg/m2, with body weight ≥ 50 kg
Inclusion Criteria (hepatic impairment groups):
- Confirmed liver disease
- Stable comorbidities are allowed as long as generally considered healthy
- Subjects with hepatic impairment must meet the following laboratory values:
- Aspartate transaminase (AST) ≤ 5 x ULN
- Alanine transaminase (ALT) ≤ 5 x ULN
- Total bilirubin ≤ 3 x ULN (≤ 5 x XULN for subjects with severe hepatic impairment [group 4])
- Calculated creatinine clearance (using Cockcroft-Gault formula) ≥ 45 mL/min
- Platelets > 50 x 10^9/L. Subjects with severe hepatic impairment can be enrolled if platelet count > 40 x 10^9/L
Exclusion Criteria (all groups):
- History or presence of clinically significant ECG abnormalities or clinically significant cardiovascular disease
- Immunocompromised subjects, including HIV
- Use of drugs known to affect CYP3A4
- Use of QT-prolonging drugs
- Use of any other drugs, unless they are required to treat the hepatic impairment subject's disease
- Use of proton pump inhibitors (PPI) medications within 7 days prior to dosing and during the current study until last day of confinement
Exclusion Criteria (normal hepatic function group):
- A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
Exclusion Criteria (hepatic impairment groups):
- Active Grade 3 or 4 hepatic encephalopathy within 4 weeks of study entry
- Clinical evidence of severe ascites
- Ascites requiring paracentesis within 3 weeks prior to dosing
Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- University of Miami Miller School of Medicine Clinical Resea Oncology
- Clinical Pharmacology of Miami, LLC.
- Orlando Clinical Research Center
- DaVita Clinical Research
- Duke University Medical Center Oncology
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Normal hepatic function
Mild hepatic impairment
Moderate hepatic impairment
Severe hepatic impairment
Arm Description
Subjects with normal hepatic function
Subjects with mild hepatic impairment
Subjects with moderate hepatic impairment
Subjects with severe hepatic impairment
Outcomes
Primary Outcome Measures
AUClast of INC280
INC280 pharmacokinetic parameters
AUCinf of INC280
INC280 pharmacokinetic parameters
Cmax of INC280
INC280 pharmacokinetic parameters
Tmax of INC280
INC280 pharmacokinetic parameters
T1/2 of INC280
INC280 pharmacokinetic parameters
CL/F of INC280
INC280 pharmacokinetic parameters
Vz/F of INC280
INC280 pharmacokinetic parameters
Secondary Outcome Measures
Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results)
Safety
Unbound fraction and AUClast based on unbound concentration in plasma
To assess the plasma protein binding of INC280
Unbound fraction and AUCinf based on unbound concentration in plasma
To assess the plasma protein binding of INC280
Unbound fraction and Cmax based on unbound concentration in plasma
To assess the plasma protein binding of INC280
Unbound fraction and Tmax based on unbound concentration in plasma
To assess the plasma protein binding of INC280
Unbound fraction and T1/2 based on unbound concentration in plasma
To assess the plasma protein binding of INC280
Unbound fraction and CL/F based on unbound concentration in plasma
To assess the plasma protein binding of INC280
Unbound fraction and Vz/F based on unbound concentration in plasma
To assess the plasma protein binding of INC280
Full Information
NCT ID
NCT02474537
First Posted
June 9, 2015
Last Updated
December 8, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02474537
Brief Title
INC280 in Healthy Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function
Official Title
An Open Label, Single-dose, Multi-center, Parallel-group, Two-staged Study to Evaluate Pharmacokinetics of Oral cMET Inhibitor INC280 in Non-Cancer Subjects With Impaired Hepatic Function and Non-Cancer Subjects With Normal Hepatic Function
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
June 12, 2015 (Actual)
Primary Completion Date
August 14, 2017 (Actual)
Study Completion Date
September 12, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase I, multi-center, open-label, single oral dose, parallel group study to evaluate the pharmacokinetics and safety of INC280 in non-cancer subjects with impaired hepatic function and non-cancer subjects with normal hepatic function.The study population will be healthy male and postmenopausal or sterile female subjects who meet all of the inclusion and none of the exclusion criteria. Subjects will be assigned to groups according to their hepatic function: normal (Group 1), mild (Group 2), moderate (Group 3), and severe (Group 4) impairment. This study consists of a two-staged design with interim analysis. In Stage 1, subjects in Groups 1, 2 and 3 will be enrolled. Upon completion of Stage 1, an interim analysis will be conducted. Depending on the results of the analysis, either the study will conclude with no further enrollment or Stage 2 will commence with enrollment of Group 4.
A minimum of 6 evaluable subjects per group will be enrolled.Once enrolled in the study, participants will be confined to the facility for 4 days, given a single dose of INC280 and monitored for pharmacokinetic and safety assessments.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
hepatic impairment,, INC280,, Oral cMET Inhibitor,, Non-Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal hepatic function
Arm Type
Experimental
Arm Description
Subjects with normal hepatic function
Arm Title
Mild hepatic impairment
Arm Type
Experimental
Arm Description
Subjects with mild hepatic impairment
Arm Title
Moderate hepatic impairment
Arm Type
Experimental
Arm Description
Subjects with moderate hepatic impairment
Arm Title
Severe hepatic impairment
Arm Type
Experimental
Arm Description
Subjects with severe hepatic impairment
Intervention Type
Drug
Intervention Name(s)
INC280
Intervention Description
Single 200 mg dose INC280
Primary Outcome Measure Information:
Title
AUClast of INC280
Description
INC280 pharmacokinetic parameters
Time Frame
Up to 72 hours post-dose
Title
AUCinf of INC280
Description
INC280 pharmacokinetic parameters
Time Frame
Up to 72 hours post-dose
Title
Cmax of INC280
Description
INC280 pharmacokinetic parameters
Time Frame
Up to 72 hours post-dose
Title
Tmax of INC280
Description
INC280 pharmacokinetic parameters
Time Frame
Up to 72 hours post-dose
Title
T1/2 of INC280
Description
INC280 pharmacokinetic parameters
Time Frame
Up to 72 hours post-dose
Title
CL/F of INC280
Description
INC280 pharmacokinetic parameters
Time Frame
Up to 72 hours post-dose
Title
Vz/F of INC280
Description
INC280 pharmacokinetic parameters
Time Frame
Up to 72 hours post-dose
Secondary Outcome Measure Information:
Title
Adverse events based on the CTCAE v4.03 grade (severity) and frequency, and other safety data (e.g., ECG, laboratory results)
Description
Safety
Time Frame
Up to 30 days
Title
Unbound fraction and AUClast based on unbound concentration in plasma
Description
To assess the plasma protein binding of INC280
Time Frame
3 hours post-dose
Title
Unbound fraction and AUCinf based on unbound concentration in plasma
Description
To assess the plasma protein binding of INC280
Time Frame
3 hours post-dose
Title
Unbound fraction and Cmax based on unbound concentration in plasma
Description
To assess the plasma protein binding of INC280
Time Frame
3 hours post-dose
Title
Unbound fraction and Tmax based on unbound concentration in plasma
Description
To assess the plasma protein binding of INC280
Time Frame
3 hours post-dose
Title
Unbound fraction and T1/2 based on unbound concentration in plasma
Description
To assess the plasma protein binding of INC280
Time Frame
3 hours post-dose
Title
Unbound fraction and CL/F based on unbound concentration in plasma
Description
To assess the plasma protein binding of INC280
Time Frame
3 hours post-dose
Title
Unbound fraction and Vz/F based on unbound concentration in plasma
Description
To assess the plasma protein binding of INC280
Time Frame
3 hours post-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria (all groups):
Female subjects must be postmenopausal or sterile
Good health, as determined by absence of clinically significant findings in medical history, physical examination, vital signs, and ECGs, unless it is consistent with known clinical disease for hepatic impairment subjects
Adequate organ function and normal laboratory tests, unless it is consistent with known clinical disease for hepatic impairment subjects
Body Mass Index (BMI) of 18- 36 kg/m2, with body weight ≥ 50 kg
Inclusion Criteria (hepatic impairment groups):
Confirmed liver disease
Stable comorbidities are allowed as long as generally considered healthy
Subjects with hepatic impairment must meet the following laboratory values:
Aspartate transaminase (AST) ≤ 5 x ULN
Alanine transaminase (ALT) ≤ 5 x ULN
Total bilirubin ≤ 3 x ULN (≤ 5 x XULN for subjects with severe hepatic impairment [group 4])
Calculated creatinine clearance (using Cockcroft-Gault formula) ≥ 45 mL/min
Platelets > 50 x 10^9/L. Subjects with severe hepatic impairment can be enrolled if platelet count > 40 x 10^9/L
Exclusion Criteria (all groups):
History or presence of clinically significant ECG abnormalities or clinically significant cardiovascular disease
Immunocompromised subjects, including HIV
Use of drugs known to affect CYP3A4
Use of QT-prolonging drugs
Use of any other drugs, unless they are required to treat the hepatic impairment subject's disease
Use of proton pump inhibitors (PPI) medications within 7 days prior to dosing and during the current study until last day of confinement
Exclusion Criteria (normal hepatic function group):
A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result
Exclusion Criteria (hepatic impairment groups):
Active Grade 3 or 4 hepatic encephalopathy within 4 weeks of study entry
Clinical evidence of severe ascites
Ascites requiring paracentesis within 3 weeks prior to dosing
Other protocol-defined inclusion/exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
NovartisPharmaceuticals
Organizational Affiliation
NovartisPharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Miami Miller School of Medicine Clinical Resea Oncology
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Clinical Pharmacology of Miami, LLC.
City
Miami
State/Province
Florida
ZIP/Postal Code
33142
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32086
Country
United States
Facility Name
DaVita Clinical Research
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Duke University Medical Center Oncology
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34046915
Citation
Chen X, Cui X, Pognan N, Quinlan M, Kapoor S, Rahmanzadeh G, Giovannini M, Marbury TC. Pharmacokinetics of capmatinib in participants with hepatic impairment: A phase 1, open-label, single-dose, parallel-group study. Br J Clin Pharmacol. 2022 Jan;88(1):91-102. doi: 10.1111/bcp.14929. Epub 2021 Jun 18.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17140
Description
Results for CINC280A2106 can be found on the Novartis Clinical Trial Results website
Learn more about this trial
INC280 in Healthy Subjects With Impaired Hepatic Function and Subjects With Normal Hepatic Function
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